P1321: INCIDENCE AND IMPACT OF GRAFT-VERSUS-HOST DISEASE (GVHD) IN PATIENTS OVER 60 YEARS OF AGE UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT). RETROSPECTIVE EXPERIENCE OF TWO SPANISH CENTERS
Authors: M. Baile, M. Hidalgo Soto, S. Marcos Asensio, M. Cabrero Calvo, R. Martínez Fernández, A. Avendaño Pita, A. Á. Martín López, A. Cabero Martínez, M. Cortés Rodríguez, E. Pérez López, L. López Corral, F. Sánchez Guijo, L. Vázquez López, M. D. Caballero Barrigón
Journal: HemaSphere (2022)

Background: Acute and chronic GVHD are of the main complications of HSCT and their frequency and impact in patients over 60 years is not fully understood. Aims: To describe their incidence and to analyze the influence of age and modalities of HSCT on their appearance, as well their impact on survival. Methods: Retrospective study of 142 patients over 60 years with hematological neoplasms undergoing allogeneic HSCT Results: Patient characteristics and survival curves are shown in Image 1. Acute GVHD was the most common complication (incidence of 72.5%) although only 10.5% were severe cases (Grades 3-4). It was an early complication (median onset 28 days). A higher incidence was observed in unrelated donor transplant recipients (82%/100% if mismatch) compared to related (62%) and haploidentical (66%) (p-value 0.28). There were no differences with the intensity of conditioning (Myeloblative 78.5% and reduced intensity 72%) although the highest severe cases was observed of myeloablative unrelated transplant (66.5%; p-value 0.03). The incidence was higher with older age (91% in >70 years; 74% in 65-69 and 69% in <65; p-value 0.15) and in CMV serological discrepancy (88.5% in recipient+/donor-; p-value 0.19). In relation to immunosuppression, there was a higher incidence with Tacrolimus/Sirolimus (82%) and less with Cyclosporine/ Mycophenolate of Mofetil (MMF) (40%): p-value 0.2; however they were the regimen most and least used, respectively. Severe aGVHD had an unfavorable impact on survival: median Progression-Free Survival (PFS) of 5 months vs 25 and 27 if not aGVHD or if mild (p-value 0.008/HR 2.3 (CI 1.2-4.6)); and median overall survival (OS) of 7 months vs 40 and 45 if not aGVHD or if mild (p-value 0.002/HR 2.6 (CI 1.3-5.4)). Severe aGVHD was associated with a higher frequency of infectious complications: more CMV reactivation (73.5% vs 37.5% if mild and 25.5% if not aGVHD; p-value 0.005), CMV disease (40% vs 4.5% if mild or 0% if not aGVHD; p-value <0.001), bacterial sepsis (60% vs 13.5% if mild or 18% if not aGVHD; p-value <0.001) and invasive fungal infection (26.5% vs 1 and 5% if mild or not aGVHD; p-value 0.001). And, these complications were associated with worse survival (median OS of 6 months vs 34 at the global serie). Together (aGVHD and related infections) caused 15% of deaths and were the first cause of mortality related to treatment. Chronic GVHD was less frequent (31%), only 13.5% were severe cases, and it occurred later (median onset of 7.5 months). A higher incidence was in unrelated-mismatch donor recipients (60%; p-value 0.04) and lower in haploidentical (15%) and no differences were observed with the intensity of conditioning (mieloablatyve 35,5% and reduced intensity 30.5%). There was a higher incidence with older age (36.5% in >70 years; 33.5% in 65-69 and 28.5% in <65; p-value 0.61) and if serological CMV discrepancy recipient -/donor+ (50%; p-value 0.83). The incidence was again higher with Tacrolimus / Sirolimus regimen and the lowest with Tacrolimus/MMF/Ciclofosfamide-post-transplant (p-value 0.09). Mild-moderate cGVHD had a protective effect on survival: median PFS of 38 months vs 8 if not cGVHD (p-value 0.03/HR 0.55 (CI 0.32-0.94)); and median OS of 19 months vs 11 if not cGVHD (p-value 0.001/HR 0.47 (CI 0.27-0.84)). Image:Summary/Conclusion: GVHD is a very relevant complication: the aGVHD due to its high incidence and impact on survival and appearance of infectious complications; and the protective effect of the cGVHD. Although a higher incidence is observed with older age, longer series and comparative studies are needed to confirm these results.